Key pointsr Recent studies have shown that some of the deleterious effects of a high-salt (HS) diet are independent of elevated blood pressure and are associated with impaired endothelial function.r Increased generation of cyclo-oxygenase (COX-1 and COX-2)-derived vasoconstrictor factors and endothelial activation may contribute to impaired vascular relaxation during HS loading.r The present study aimed to assess the regulation of microvascular reactivity and to clarify the role of COX-1 and COX-2 in normotensive subjects on a short-term HS diet.r The present study demonstrates the important role of COX-1 derived vasoconstrictor metabolites in regulation of microvascular blood flow during a HS diet.r These results help to explain how even short-term HS diets may impact upon microvascular reactivity without changes in blood pressure and suggest that a vasoconstrictor metabolite of COX-1 could play a role in this impaired tissue blood flow. AbstractThe present study aimed to assess the effect of a 1-week high-salt (HS) diet on the role of cyclo-oxygenases (COX-1 and COX-2) and the vasoconstrictor prostaglandins, thromboxane A 2 (TXA 2 ) and prostaglandin F 2α (PGF 2α ), on skin microcirculatory blood flow, as well as to detect its effect on markers of endothelial activation such as soluble cell adhesion molecules. Young women (n = 54) were assigned to either the HS diet group (N = 30) (ß14 g day -1 NaCl ) or low-salt (LS) diet group (N = 24) (<2.3 g day -1 NaCl ) for 7 days. Post-occlusive reactive hyperaemia (PORH) in the skin microcirculation was assessed by laser Doppler flowmetry. Plasma renin activity, plasma aldosterone, plasma and 24 h urine sodium and potassium, plasma concentrations of TXB 2 (stable TXA 2 metabolite) and PGF 2α , soluble cell adhesion molecules and blood pressure were measured before and after the diet protocols. One HS diet group subset received 100 mg of indomethacin (non-selective COX-1 and COX-2 inhibitor), and another HS group subset received 200 mg of celecoxib (selective COX-2 inhibitor) before repeating laser Doppler flowmetry measurements. Blood pressure was unchanged after the HS diet, although it significantly reduced after the LS diet. Twenty-four hour urinary sodium was increased, and plasma renin activity and plasma aldosterone levels were decreased after the HS diet. The HS diet significantly impaired PORH and increased TXA 2 but did not change PGF 2α levels. Indomethacin restored microcirculatory blood flow and reduced TXA 2 . By contrast, celecoxib decreased TXA 2 levels but had no significant effects on blood flow. Restoration of of PORH by indomethacin during a HS diet suggests an important role of COX-1 derived vasoconstrictor metabolites in the regulation of microvascular blood flow during HS intake.

Background and aims The hypothesis of this study was that microvascular flow-induced dilation (FID) and acetylcholine-induced dilation (AChID) is impaired in visceral (VAT) compared to subcutaneous adipose tissue (SAT) arterioles in morbidly obese women. Additional aim was to determine the mechanisms contributing to FID and AChID in VAT and SAT arterioles. Methods and results Arterioles were obtained from SAT and VAT biopsies from women (BMI>35 kg/m2) undergoing bariatric surgery. Microvessels were cannulated for reactivity measurements in response to flow (pressure gradients of 10–100 cmH2O) and to acetylcholine (ACh;10−9–10−4 M) with and without Nω-nitro-L-arginine methyl ester (L-NAME), indomethacin (INDO), and PEG-catalase. Nitric oxide (NO)and hydrogen peroxide (H2O2) generation were detected in arterioles by fluorescence microscopy. FID and AChID of arterioles from VAT were reduced compared to SAT arterioles. In SAT arterioles, L-NAME, INDO, and PEG-catalase significantly reduced FID and AChID but had no effect individually on VAT arterioles’ vasodilator reactivity. INDO+L-NAME reduced FID in VAT arterioles. NO-fluorescence was greater in arterioles from SAT compared to VAT arterioles. Vascular H2O2 generation during flow was similar in both VAT and SAT. Conclusion Our results suggest that VAT arterioles display reduced vasodilator reactivity to flow and ACh compared to SAT arterioles, mediated by different regulatory mechanisms in human obesity.

These data suggest that high salt intake reduces brachial artery endothelial function and switches the mediator of vasodilation in the microcirculation to a non-nitric oxide-dependent mechanism in healthy adults and acute exercise may switch the dilator mechanism back to nitric oxide during high salt diet.

Apolipoprotein E (apoE) is widely expressed in mammalian tissues and one of the important tissue-specific effects is the atheroprotection ascribed to macrophage-derived apoE in the arterial wall. However, underlying mechanisms are not well understood. In this study, using subcellular fractionation, confocal microscopy and co-immunoprecipitation, we demonstrate that macrophage-derived apoE is internalized by endothelial cells and impacts the subcellular distribution/interaction of caveolin-1 and eNOS. Addition of apoE disrupts the heteromeric complex formed between caveolin-1 and eNOS, and increases nitric oxide (NO) production. Sterol and oxysterol enhance endothelial caveolin-1/eNOS interaction and suppress NO production but these effects are reversed by apoE. Silencing endothelial caveolin-1 attenuates apoE induced NO production establishing the importance of Cav-1/eNOS interaction for the increment in endothelial NO for the apoE effect. Consistent with these observations, macrophage-derived apoE significantly improves vasodilation to acetylcholine in resistance arteries isolated from adipose tissue of obese humans. We conclude that macrophage-derived apoE enhances endothelial NO production by disrupting the inhibitory interaction of eNOS with caveolin-1. These results establish a novel mechanism by which apoE modulates endothelial cell function.

The control of arterial pressure is a complex interaction of the long- and short-term influences of hormones, local vascular factors, and neural mechanisms. The autonomic nervous system and its sympathetic arm play important roles in the regulation of blood pressure, and overactivity of sympathetic nerves may have an important role in the development of hypertension and related cardiovascular disorders. The baroreceptor system opposes either increases or decreases in arterial pressure, and the primary purpose of the arterial baroreflex is to keep blood pressure close to a particular set point over a relatively short period of time. The ability of the baroreflex to powerfully buffer acute changes in arterial pressure is well established, but the role of the arterial baroreceptor reflex in long-term control of arterial pressure has been a topic of many debate and controversy for decades. The sympathetic nervous system and arterial baroreceptor reflex control of renal sympathetic nerve activity has been proposed to play a role in long-term control of arterial pressure. The aim of this paper has been to review the postulated role of sympathetic activation.

Objectives. To assess the effect of Red Bull© on (1) blood glucose and catecholamine levels, (2) cardiovascular and respiratory function changes before, during, and after exercise, (3) reaction time, (4) cognitive functions, and (5) response to mental stress test and emotions in young healthy individuals (N=38). Methods. Heart rate (HR) and arterial blood pressure (ABP), blood glucose, adrenaline, and noradrenalin plasma levels were measured before and after Red Bull© intake. Participants were subjected to 4 different study protocols by randomized order, before and 30 minutes after consumption of 500 mL of Red Bull©. Results. Mean ABP and HR were significantly increased at rest after Red Bull© intake. Blood glucose level and plasma catecholamine levels significantly increased after Red Bull© consumption. Heart rate, respiration rate, and respiratory flow rate were significantly increased during exercise after Red Bull© consumption compared to control condition. Intake of Red Bull© significantly improved reaction time, performance in immediate memory test, verbal fluency, and subject's attention as well as performance in mental stress test. Conclusion. This study demonstrated that Red Bull© has beneficial effect on some cognitive functions and effect on cardiovascular and respiratory system at rest and during exercise by increasing activity of the sympathetic nervous system.

Objective: To determine the effect of AT1 receptor antagonism on skin microcirculation and plasma level of thromboxane A₂ (TXA₂). Methods: Healthy women (n=20) maintained 7 days low salt (LS) diet (intake <40 mmol Na/day) without (LS) or together with 50 mg/per day of losartan (a selective AT1 receptor inhibitor) (LS diet+losartan group). Laser Doppler flowmetry (LDF) measurements of changes in post occlusive hyperemic blood flow, plasma concentration of stable TXA₂ metabolite thromboxane B₂ (TXB₂) and plasma renin activity (PRA) aldosterone concentration, electrolytes (Na⁺, K⁺), as well as blood pressure and heart rate were determined before and after study protocols. Results: PRA and aldosterone increased significantly after 7 days of both LS diet and LS diet+losartan. LS diet or LS diet+losartan administrations had no significant effect on post-occlusion hyperemia While there was no change in TXB₂ after LS diet TXB₂ significantly increased after one week of LS+losartan compared to control levels (cTXB2 pg/mL control 101±80 vs. LS diet+losartan 190±116, p<0.05). Conclusion: These data suggest that inhibition of AT1 receptors could lead to activation of AT2 receptors, which maintain hyperemia, despite the increased level of vasoconstrictor TXA₂. These findings also suggest an important role of crosstalk between renin-angiotensin system (RAS) and arachidonic acid metabolites in the regulation of microcirculation under physiological conditions.

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